1. Field of the Invention
This invention relates to treatment of diseases and/or disorders of the posterior segment of the eye and more particularly to the treatment of disorders arising from a decrease or failure of blood perfusion to the posterior ocular structures.
2. Description of the Prior Art
The mammalian eye is a generally spherical structure that performs its visual function by forming an image of an exterior illuminated object on a photosensitive tissue, the retina. The basic supporting structure for the functional elements of the eye is the generally spherical tough, white outer shell, the sclera, which is comprised principally of collagenous connective tissue and is kept in its spherical shape by the internal pressure of the eye. The anterior portion of the sclera supports and contains the elements that perform the function of focusing the incoming light, i.e., the cornea and crystalline lens, and the function of regulating the intensity of the light entering the eye, i.e., the iris. The posterior portion of the globe supports the retina and associated tissues. In the posterior portion of the globe immediately adjacent the interior surface of the sclera lies the choroid, a thin layer of pigmented tissue liberally supplied with blood vessels. The portion of the choroid adjacent its interior surface is comprised of a network of capillaries, the choriocapillaris, which is of importance in the supply of oxygen and nutrients to the adjacent layers of the retina. Immediately within the choroid lies the retina, which is the innermost layer of the posterior segment of the eye and receives the image formed by the refractive elements in the anterior portion of the globe. The photoreceptive rod and cone cells of the retina are stimulated by light falling on them and pass their sensations via the retinal ganglia to the brain.
Retinal function and health is dependent on two independent blood supplies. The outer portion of the retina, adjacent to the choroid, is nurtured primarily by the choriocapillaris of the choroid, while inner retinal layers receive their blood supply mainly via branches of the central retinal artery. Accordingly, both blood supplies are must be intact for proper perfusion of the retina, and one of them cannot substitute for the other.
Occlusive diseases or disorders of blood vessels servicing the retina affect the inner layers of the sensory retina most significantly and therefore concern blood vessels, i.e., arterioles and capillaries, that receive their blood supply from the central retinal artery. Normal perfusion of retinal tissues requires that vascular pressure in the retinal arteries, capillaries, and veins exceed the intraocular pressure of the eye in order to prevent the retinal vascular system from collapsing. Diseases or disorders that restrict or stop retinal blood perfusion can be localized and unique to the retina or reflective of systemic vascular diseases such as atherosclerosis. Regardless of etiology, compromised blood perfusion of retinal arteries to the extent that vascular pressure within the retina structure is less than IOP causes these arteries to collapse leading to retinal ischemia with accompanying coagulative necrosis of inner retinal layers and loss of visual function in the ischemic portions of the retina.
The prognosis of such a disorder is related to the cause(s), degree of obstruction and length of time the occlusion persists. Occlusions resulting from the effects of systemic vascular problems, such as atherosclerotic cardiovascular disease and hypertension, can cause entrapment of cholesterol emboli in the retinal artery causing lasting visual field defects. In contrast, episodes of occlusion by platelet emboli are typically brief, leaving no visual abnormality. In any case, treatment directed toward alleviating the nonperfusion condition having an acute onset needs to be effective within 3-4 hours following the episode; otherwise, irreversible visual defects will result.
Historically, patients with retinal artery obstruction have been treated by administration of 100% oxygen or carbogen (95% oxygen, 5% carbon dioxide) in an attempt to improve retinal oxygenation. However, because of irreversible adverse side effects associated with administering pure or high concentration oxygen, the duration of this therapy must be limited. Additionally, while gas therapy is designed to oxygenate retinal tissue, it does not promote blood perfusion per se. Clearly, because of (i) the need to initiate this sophisticated response treatment quickly, and (ii) its potential side effects, there is need for a more readily available, practical and safer treatment regimen that focuses on prevention of the episode rather than responding to the episode.
In general, retinal disorders characterized by retinal ischemia and therefore responsive to improved blood flow include, but are not limited to:
(i) diabetic retinopathy PA1 (ii) central retinal artery occlusion PA1 (iii) central retinal vein occlusion and resultant degenerative diseases of the retinal venous endothelium PA1 (iv) senile macular degeneration PA1 (v) ischemic optic neuropathies PA1 (vi) transient central retinal occlusion
Hitherto, certain treatments have been used with some success in delaying the progression of ophthalmic deterioration or even partially reversing the course of these diseases. Systemic drugs that increase the blood flow to the retina have been found to have some effect in alleviating the progression of such conditions as diabetic retinopathy. In particular, systemic, e.g., oral, administration of calcium channel blocking agents has been found to be of some benefit in treating conditions due to poor blood flow in the posterior segment of the eye. However, the systemic administration of vasoactive drugs in order to treat a condition specific to certain structures of the eye is subject to the evident disadvantage that undesirable systemic side effects may be induced. Hitherto it has not been known that topical administration of calcium channel blocking agents can improve blood flow to the posterior segment of the eyeball and thereby arrest or alleviate the deterioration of vision associated with retinal conditions caused by deficient retinal blood flow.
Although it is well known to apply topical medications to treat ophthalmic disorders caused by dysfunction of tissues in the anterior region of the eye, topical application of medication has not been generally found effective to treat ophthalmic pathologic conditions of tissues and structures located in the posterior region of the eye.
Accordingly, a need has continued to exist for a method-of treating diseases and disorders of the posterior segment of the eye caused by poor blood flow by topical administration of an effective ophthalmic medicament.